The present invention relates to an oral pharmaceutical composition comprising a compound having antifungal activity and in which the problems of low bioavailability, due to the poor solubility of antifungal compounds in an aqueous medium, are solved.
The present invention also relates to a method for obtaining said oral pharmaceutical composition that has advantages over conventional methods.
The problems of solubility associated to the chemical structures of azoles such as itraconazole and saperconazole, compounds respectively described in U.S. Pat. Nos. 4,267,179 and 4,916,134, try to be solved by preparing different pharmaceutical forms on the base of the different administration methods.
It is known that the solubility of a compound can increase when it is added to an hydrophilic polymer and apply the mixture on an inert core. A formulation is obtained that improves remarkably the bioavailability of the compound.
In patent EP 658103 (published in Spain as ES 2097536 T3) pellets of itraconazole and saperconazole prepared on the basis of this technology. It discloses the preparation of a solution in ethanol and methylene chloride of the antifungal compound and the hydrophilic polymer hydroxypropylmethylcellulose (HPMC) which is sprayed in a fluidized bed on inert cores having a size between 600 and 700 xcexcm. Once the spraying process is finished, the beads are dried in the same apparatus during ten minutes at a temperature of 50-55xc2x0 C., but thereafter they must be introduced in a vacuum drier for about 36 hours at a temperature of 80xc2x0 C. The dry cores are sieved and are subjected to a second coating process in order to form a second layer with a solution of polyethylene glycol 20000 (PEG 20000) in a fluidized bed. When the process is finished, the beads are dried in the apparatus for 10 minutes at 50-55xc2x0 C. and then dry air at 20-25xc2x0 C. is supplied to them during 5-15 minutes. When the drying process is finished, they are stored in suitable containers.
EP 658103 teaches that the second coating layer with PEG 20000, which is a sealing coating layer, is applied in order to prevent pellets from adhering, and that it is necessary to have inert cores of a size between 600 and 700 xcexcm in order to avoid drying problems and pellet aggregation. According to EP 658103, inert cores having a larger size involve a smaller specific surface, whereby the coating layers need to be very thick and thus difficult to dry, while if the inert core size is too small it gives rise to a thin coating layer, easy to dry but that can undergo agglomeration phenomena during the coating step.